Shelf-stable formulations of benzoyl peroxide and methods of producing same

Abstract

Disclosed herein are shelf-stable formulations comprising benzoyl peroxide in a formulation effective to reduce or prevent degradation of the benzoyl peroxide to benzene. Further provided herein are methods of preventing or reducing degradation of benzoyl peroxide to benzene in a drug product, as well as methods of identifying drug products containing benzoyl peroxide that form high levels of benzene.

What is claimed is: 
     
         1 . A kit comprising:
 (a) a first container or a plurality of first containers containing therein benzoyl peroxide, wherein the benzoyl peroxide is in substantially pure form or is in a formulation effective to reduce or prevent degradation of the benzoyl peroxide to benzene;   (b) a second container or a plurality of second containers containing therein at least one ingredient; and   (c) instructions for combining the benzoyl peroxide with the at least one ingredient to generate a compounded benzoyl peroxide drug product.   
     
     
         2 . The kit of  claim 1 , wherein, when the first container or plurality of first containers is heated to 70° C. for 7 days or more, a concentration of benzene in the formulation is less than about 2 parts per million (2 ppm). 
     
     
         3 . The kit of  claim 1 , wherein, when the compounded benzoyl peroxide drug product is heated to 70° C. for 7 days or more, a concentration of benzene in the compounded benzoyl peroxide drug product is less than about 2 ppm. 
     
     
         4 . The kit of  claim 1 , wherein the at least one ingredient is selected from the group consisting of: a formulation, an inactive ingredient, an active ingredient other than benzoyl peroxide, a solvent, a stabilizing agent, a capsule, a particle, and any combination thereof. 
     
     
         5 . The kit of  claim 4 , wherein the active ingredient other than benzoyl peroxide is selected from the group consisting of: an antibiotic, a retinoid or retinoid-like compound, an anti-inflammatory agent, a diuretic, and any combination thereof. 
     
     
         6 . The kit of  claim 1 , wherein the compounded benzoyl peroxide drug product is for use by an individual within a period of time after generation of the compounded benzoyl peroxide drug product. 
     
     
         7 . The kit of  claim 6 , wherein the period of time is selected from the group consisting of: 36 months or less, 24 months or less, 18 months or less, 12 months or less, 9 months or less, 6 months or less, 3 months or less, 90 days or less, 60 days or less, 45 days or less, 30 days or less, 15 days or less, 10 days or less, 7 days or less, 5 days or less, 72 hours or less, 48 hours or less, 24 hours or less, 12 hours or less, 1 hour or less, 30 minutes or less, 10 minutes or less, and 5 minutes or less. 
     
     
         8 . The kit of  claim 1 , wherein the compounded benzoyl peroxide drug product is for use by an animal. 
     
     
         9 . The kit of  claim 1 , wherein the compounded benzoyl peroxide drug product is for use by a human. 
     
     
         10 . The kit of  claim 1 , wherein the benzoyl peroxide in substantially pure form has a purity selected from the group consisting of: greater than about 90%, greater than about 95%, greater than about 97%, greater than about 98%, greater than about 99%, and greater than about 99.9%. 
     
     
         11 . The kit of  claim 1 , wherein the benzoyl peroxide is in the form of a crystalline powder. 
     
     
         12 . The kit of  claim 1 , wherein, when the compounded benzoyl peroxide drug product is subjected to stability testing following guidelines from a regulatory agency in a jurisdiction in which the compounded benzoyl peroxide drug product is to be registered or sold, the concentration of benzene in the compounded benzoyl peroxide drug product is less than about 2 ppm, less than about 1 ppm, less than about 0.5 ppm, less than about 0.1 ppm, undetectable, or any combination thereof. 
     
     
         13 . The kit of  claim 1 , wherein the kit further comprises packaging which prevents or reduces the degradation of benzoyl peroxide to benzene. 
     
     
         14 . The kit of  claim 13 , wherein the packaging prevents or reduces exposure of the benzoyl peroxide to light. 
     
     
         15 . The kit of  claim 1 , further comprising instructions to store the first container or plurality of first containers, the second container or plurality of second containers, the compounded benzoyl peroxide drug product, or any combination thereof, at a temperature selected from the group consisting of: at or below about 25° C., at or below about 20° C., at or below about 15° C., at or below about 10° C., at or below about 4° C., at or below about 0° C., at or below about −20° C., at or below about −70° C., and any combination thereof. 
     
     
         16 . The kit of  claim 1 , wherein an amount or concentration of benzoyl peroxide in the compounded benzoyl peroxide drug product is an amount or concentration of benzoyl peroxide effective for treating a skin condition in a subject. 
     
     
         17 . The kit of  claim 16 , wherein the concentration of benzoyl peroxide in the compounded benzoyl peroxide drug product is from about 2.5% w/w to about 10% w/w. 
     
     
         18 . The kit of  claim 17 , wherein the skin condition is acne vulgaris. 
     
     
         19 . The kit of  claim 1 , wherein the compounded benzoyl peroxide drug product is a lotion, a cream, a gel, a jelly, a foam, a pad, a wipe, a solution, a bar, or a liquid. 
     
     
         20 . A method of producing a compounded benzoyl peroxide drug product using the kit of  claim 1 , the method comprising: mixing or combining an amount of the benzoyl peroxide from the first container or plurality of first containers with an amount of the at least one ingredient from the second container or plurality of second containers to form the compounded benzoyl peroxide drug product, such that the benzoyl peroxide is present in the compounded benzoyl peroxide drug product in an amount or concentration effective to treat a disease, a disorder, or a condition of a subject.